Long noncoding RNA X-inactive specific transcript (lncRNA XIST) inhibits hepatic insulin resistance by competitively...

Area of Science:

• Molecular Biology
• Genetics
• Endocrinology

Background:

• Insulin resistance (IR) is a complex metabolic disorder characterized by impaired insulin signaling.
• Long noncoding RNAs (lncRNAs) play crucial roles in regulating gene expression and cellular functions.
• The specific role of lncRNA XIST in hepatic IR remains to be fully elucidated.

Purpose of the Study:

• To investigate the role and molecular mechanism of lncRNA XIST in hepatic insulin resistance (IR) in vitro.
• To explore the interaction between lncRNA XIST, miR-182-5p, and IGF-1R in the context of IR.
• To determine the potential of the lncRNA XIST/miR-182-5p axis as a therapeutic target for IR.

Main Methods:

• Establishment of an in vitro IR model using LX-2 cells.
• Quantification of gene and protein expression levels using qRT-PCR and Western blot.
• Detection of glucose uptake and signaling pathway activation.
• Prediction and experimental validation of molecular interactions using bioinformatics and molecular assays.
• Rescue experiments to confirm the functional role of miR-182-5p.

Main Results:

• LncRNA XIST expression was downregulated, while miR-182-5p was upregulated in IR cells.
• Overexpression of lncRNA XIST enhanced insulin sensitivity by increasing IGF-1R and glucose uptake, while decreasing gluconeogenic enzymes (G6Pase, PEPCK) and activating the PI3K/Akt pathway.
• LncRNA XIST acted as a molecular sponge for miR-182-5p, and miR-182-5p directly targeted IGF-1R.
• MiR-182-5p mimic reversed the effects of lncRNA XIST overexpression on IR cells.

Conclusions:

• The lncRNA XIST/miR-182-5p axis plays a critical role in alleviating hepatic IR.
• This axis functions through the regulation of the IGF-1R/PI3K/Akt signaling pathway.
• Targeting the lncRNA XIST/miR-182-5p axis represents a promising therapeutic strategy for managing hepatic IR.